title: The equine antimicrobial peptide eCATH1 is effective against the facultative intracellular pathogen Rhodococcus equi in mice.
abstract: Rhodococcus equi, the causal agent of rhodococcosis, is a major pathogen of foals and is also responsible for severe infections in immunocompromised humans. Of great concern, strains resistant to currently used antibiotics have emerged. As the number of drugs that are efficient in vivo is limited because of the intracellular localization of the bacterium inside macrophages, new active but cell-permeant drugs will be needed in the near future. In the present study, we evaluated, by in vitro and ex vivo experiments, the ability of the alpha-helical equine antimicrobial peptide eCATH1 to kill intracellular bacterial cells. Moreover, the therapeutic potential of the peptide was assessed in experimental rhodococcosis induced in mice, while the in vivo toxicity was evaluated by behavioral and histopathological analysis. The study revealed that eCATH1 significantly reduced the number of bacteria inside macrophages. Furthermore, the bactericidal potential of the peptide was maintained in vivo at doses that appeared to have no visible deleterious effects for the mice even after 7 days of treatment. Indeed, daily subcutaneous injections of 1 mg/kg body weight of eCATH1 led to a significant reduction of the bacterial load in organs comparable to that obtained after treatment with 10 mg/kg body weight of rifampin. Interestingly, the combination of the peptide with rifampin showed a synergistic interaction in both ex vivo and in vivo experiments. These results emphasize the therapeutic potential that eCATH1 represents in the treatment of rhodococcosis.
authors.affiliation: Anses, Dozulé Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, Dozulé, France.
authors.forename: Margot
authors.initials: M
authors.lastname: Schlusselhuber
authors.forename: Riccardo
authors.initials: R
authors.lastname: Torelli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martini
authors.forename: Matthias
authors.initials: M
authors.lastname: Leippe
authors.forename: Vincent
authors.initials: V
authors.lastname: Cattoir
authors.forename: Roland
authors.initials: R
authors.lastname: Leclercq
authors.forename: Claire
authors.initials: C
authors.lastname: Laugier
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.forename: Julien
authors.initials: J
authors.lastname: Cauchard
mesh_terms: D000193:Actinomycetales Infections / Q000188:drug therapy*; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002460:Cell Line; D017737:Macrophages, Peritoneal / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D016929:Rhodococcus equi / Q000187:drug effects / Q000472:pathogenicity*; D012293:Rifampin / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D012293:Rifampin